Effect of Steroids on Anti-nephrin Autoantibodies and B cells in Minimal Change Disease

Hengel, Felicitas E. ; Beldi-Ferchiou, Asma ; Sakhi, Hamza ; Liaukouskaya, Nastassia ; Dehde, Silke ; Karras, Alexandre ; Esteve, Emmanuel ; Oniszczuk, Julie ; Le Gouvello, Sabine ; Herrera Marcos, Luis (Universidad de Zaragoza) ; Joher, Nizar ; Daugas, Eric ; Zaidan, Mohamad ; El Karoui, Khalil ; Knebelmann, Bertrand ; Dao, Myriam ; Moktefi, Anissa ; Sahali, Dil ; Huber, Tobias B. ; Ollero, Mario ; Tomas, Nicola M. ; Audard, Vincent

Resumen: Introduction
The identification of autoantibodies against nephrin, a key signaling protein of the podocyte slit diaphragm, and their pathogenic role in patients with minimal change disease (MCD) has substantially changed our understanding of primary podocytopathies. However, details on underlying immune pathophysiological mechanisms such as the relation of anti-nephrin autoantibodies with immune cell subsets and therapy response remain to be determined.

Methods
In this prospective study, we evaluated blood samples from adults with newly diagnosed, biopsy-proven MCD for circulating anti-nephrin antibodies using immunoprecipitation (IP) and B-cell subpopulations by fluorescence-activated cell sorting. Samples were collected at diagnosis (t0) and after 8 weeks of steroid therapy (t1).

Results
We detected anti-nephrin antibodies in 12 of 17 (70.6%) therapy-naïve patients with MCD at t0. All 12 patients (100%) positive for anti-nephrin antibodies achieved complete remission with no anti-nephrin antibodies detectable after 8 weeks of steroid treatment (t1). Two of 5 anti-nephrin negative patients (40%) did not reach clinical remission at t1. Anti-nephrin positive patients exhibited a larger fraction of plasmablasts than anti-nephrin negative patients at t0, albeit not statistically significant. Plasmablasts, naïve B cells, and transitional B cells significantly decreased, whereas marginal zone–like B cells increased within 8 weeks of steroid treatment in anti-nephrin positive patients (t1).

Conclusion
Our study shows, for the first time, a therapeutically relevant short-term effect of steroids on the B-cell compartment and anti-nephrin antibody levels, explaining the high clinical response rate in patients with anti-nephrin-associated MCD.

Idioma: Inglés

DOI: 10.1016/j.ekir.2026.103794

Año: 2026

Publicado en: Kidney International Reports 11, 4 (2026), 103794 [11 pp.]
ISSN: 2468-0249

Tipo y forma: Article (Published version)

Área (Departamento): Área Farmacología (Dpto. Farmac.Fisiol.y Med.L.F.)